Microsatellite Instability Prognostic for Stage II Colon Cancer

Microsatellite instability has a significant impact on stage II colon cancer survival

medwireNews: Microsatellite instability (MSI) is a positive Prognostic factor for stage II colon cancer, but plays a weaker role in stage III disease outcomes, analysis of data from the PETACC-3 trial suggests.

Stage II patients with high MSI, defined as instability in at least three out of 10 tested loci, had a better outcome than those with low or no MSI regardless of whether they were randomly assigned to receive fluorouracil plus leucovorin (5-FU/LV) alone or alongside irinotecan (FOLFIRI).

However, contrary to previous research, addition of irinotecan to the chemotherapy regimen did not offer further survival benefits, say Sabine Tejpar, from Leuven University Hospital in Belgium, and co-authors.

After a median of 69.1 months, relapse-free survival (RFS) and overall survival (OS) were both significantly longer in the 86 stage II patients with high instability than in the 309 stage II patients with no or low instability, with hazard ratios of 0.26 and 0.16, respectively.

RFS was also significantly longer in the 104 stage III patients with high MSI than the 755 patients with low or no MSI (HR=0.67), but MSI status did not significantly predict OS in this population, the team reports in the Annals of Oncology.

Sabine Tejpar et al note that patients with right-sided colon cancer were five times more likely to have high MSI than those with left-sided tumours (28.7 vs 6.1%).

For left-sided carcinoma stage II patients, RFS was comparable between high and low or no MSI patients, whereas RFS was significantly better in right-sided colon cancer patients with high MSI than in those with low or no MSI.

Patients with K-Ras-mutated colon cancer were 1.5 times less likely to have high MSI than Wild-type K-Ras patients and, in turn, patients with K-ras-mutated colon cancer had better RFS and OS than those without the mutation.

In addition, patients with BRAF-mutated colon cancer were four times more likely to have high MSI than those with wild-type BRAF,but the mutation status was not prognostic. This finding was, however, “possibly limited by sample size”, the researchers comment.

“Additional parameters (including Gene expression profiling, ploidy, Methylation, and microRNA expression) have to be explored in order to more accurately define stage II patients who require adjuvant treatment and to predict which patients will respond”, the team concludes.

“Based on new emerging information, further exploratory analyses in large patients’ cohorts looking also at the impact of site, mutation profile and Genomic signatures will be necessary to further appreciate the molecular and prognostic impact of MSI status in colon cancer.”


Klingbiel D, Saridaki Z, Roth A, et al. Prognosis of stage II and III colon carcinoma treated with adjuvant 5-FU or FOLFIRI in relation to microsatellite status, results of the PETACC-3 trial. Ann Oncol; Advance online publication 30 October 2014 doi: 10.1093/annonc/mdu499

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